Cationic lipids and polymers for gene delivery

Gene therapy, aiming to eradicate causes rather than symptoms of diseases, is believed to be the therapy of the future. A new promising area for the application of gene therapy is the emerging field of regenerative medicine, where gene delivery can be used to enhance or modify cell functions in an organ/tissue or in engineered substitutes. The aim of gene therapy is to achieve the expression of transgenes in target cells, for as long as required, in an appropriately regulated form, without side effects. The main strategies for the delivery of nucleic acids in gene therapy involve viralmediated and non-viral methods. Non-viral synthetic vectors feature a high safety profile but they are still less efficient than their viral counterparts in mediating gene expression. To overcome this limitation, the incorporation of disulfide bonds has been proposed as an efficient stimuli mechanism in gene delivery to exploit the high difference in redox potential existing between the reducing intracellular space and the oxidizing extracellular milieu. Inspired by this disulfide-linker strategy, we describe herein the development of different redox-sensitive lipidic and polymeric non-viral gene delivery systems: a reducible cationic lipid, SS14, a series of reducible SS14-based liposomes and a family of redox-sensitive dithiooligopeptides.